title: AHR-10037, a non-steroidal anti-inflammatory compound of low gastric toxicity.
abstract: AHR-10037 is an anti-inflammatory compound possessing analgesic and antipyretic properties and a high therapeutic index. AHR-10037 was comparable to indomethacin in suppressing acute (Evans blue-carrageenan pleural effusion) and chronic (adjuvant-induced arthritis) inflammation. There was a delayed onset of antipyresis (yeast-induced hyperthermia in rats), analgesia (acetylcholine-induced abdominal constriction in mice) and inhibition of caster oil-induced diarrhea in rats. Antipyresis occurred 3 hours after administration of AHR-10037, 4 mg/kg, PO. vs 1 hour after administration of acetylsalicylic acid, 100 mg/kg, PO; maximum analgesic activity (ED50 = 4.1 mg/kg) occurred at 4 hours. AHR-10037 was inferior to indomethacin in suppressing castor oil-induced diarrhea in rats. The therapeutic index of AHR-10037 (relating acute anti-inflammatory potency to gastric toxicity potency relative to indomethacin) ranged from 56-91. The pharmacological profile suggests that AHR-10037 is a prodrug converted in vivo to a cyclooxygenase inhibitor.
authors.affiliation: Department of Pharmacology, A.H. Robins Co., Inc., Richmond, VA 23261-6609.
authors.forename: L F
authors.initials: LF
authors.lastname: Sancilio
authors.forename: J C
authors.initials: JC
authors.lastname: Nolan
authors.forename: L E
authors.initials: LE
authors.lastname: Wagner
authors.forename: C E
authors.initials: CE
authors.lastname: Gathright
authors.forename: D D
authors.initials: DD
authors.lastname: Droppleman
authors.forename: R S
authors.initials: RS
authors.lastname: Alphin
authors.forename: D A
authors.initials: DA
authors.lastname: Walsh
authors.forename: W J
authors.initials: WJ
authors.lastname: Welstead
mesh_terms: D000081:Acetamides / Q000494:pharmacology* / Q000633:toxicity; D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D044482:Benzeneacetamides; D001831:Body Temperature / Q000187:drug effects; D002351:Carrageenan; D002368:Castor Oil; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013272:Stomach Diseases / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D000081:Acetamides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044482:Benzeneacetamides; C065064:AHR 10037; D002368:Castor Oil; D002351:Carrageenan; D000109:Acetylcholine